Benefit-risk assessment for the Novavax COVID-19 vaccine (NVX-CoV2373).

A benefit-risk assessment of NVX-CoV2373, a vaccine to prevent COVID-19, was conducted to determine if the benefits of vaccination outweigh the risks of myocarditis/pericarditis. This analysis used data on myocarditis/pericarditis cases observed in the NVX-CoV2373 clinical studies, real-world data of mRNA COVID vaccine effectiveness against predominant SARS-CoV-2 strains in early 2023, and recent COVID-19 burden of disease data from the United States. The benefits of NVX-CoV2373 vaccination were estimated as the number of COVID-19 cases, hospitalizations, and deaths prevented. The risks of myocarditis/pericarditis cases and related hospitalizations and deaths occurring within 7 days of vaccination were also estimated. In our analysis, vaccination with NVX-CoV2373, per 100,000 vaccinated, resulted in an estimated 1805 COVID-19 cases prevented compared with an estimated 5.3 excess myocarditis/pericarditis cases. The number of COVID-19 hospitalizations and deaths prevented were also greater than vaccine-associated myocarditis/pericarditis hospitalizations and deaths. Our analysis indicates a positive benefit-risk balance for NVX-CoV2373.

The first days of diagnostic ultrasound.

The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.

A Qualitative Analysis of Clinician Perspectives of Ultrasound Biofeedback for Speech Sound Disorders.

PURPOSE: Ultrasound biofeedback therapy (UBT) is a relatively new type of technology-assisted speech-language therapy and has shown promise in remediating speech sound disorders. However, there is a current lack of understanding of the barriers and benefits that may influence the usage behavior and clinical decision making for the implementation of UBT from a clinician perspective. In this qualitative study, we explore the perspectives of speech-language pathologists (SLPs) who have used ultrasound biofeedback in programs of speech sound therapy using the unified theory of acceptance and use of technology (UTAUT) model. METHOD: Seven SLPs who had clinical experience treating speech sound disorders with UBT participated. Semistructured in-depth interviews were conducted and video-recorded. Two coders coded and categorized the transcribed data, with consensus established with a third coder. Using thematic analysis, the data were exploratorily grouped into themes along components of the UTAUT model. RESULTS: The highest number of codes was sorted into the "effort expectancy" theme, followed by "performance expectancy," "social influence," and "facilitating conditions" themes of the UTAUT model. Clinicians identified multiple perceived barriers and benefits to the use of ultrasound technology. The top identified barrier was limited accessibility, and the top benefit was the ability to visualize a client's articulatory response to cues on a display. CONCLUSIONS: Clinicians prioritized "effort expectancy" and "performance expectancy" when reflecting on the use of ultrasound biofeedback for speech sound disorders. Clinicians spoke favorably about using UBT for speech sound disorder treatment but acknowledged institutional barriers and limitations at organizational and social levels.

Effectiveness of elbasvir/grazoprevir plus ribavirin for hepatitis C virus genotype 1a infection and baseline NS5A resistance.

INTRODUCTION AND OBJECTIVES: In clinical trials, patients with hepatitis C virus (HCV) genotype (GT)1a infection and baseline resistance-associated substitutions (RASs) at amino acid positions 28, 30, 31, or 93 receiving elbasvir/grazoprevir for 12 weeks achieved lower rates of sustained virologic response (SVR) than those without baseline RASs. SVR rates in patients with RASs were improved when elbasvir/grazoprevir treatment duration was extended from 12 to 16 weeks and administered concomitantly with ribavirin. MATERIALS AND METHODS: This was a retrospective, observational analysis using electronic health record abstraction. Patients with HCV GT1a infection and RASs at positions 28, 30, 31, or 93 who were prescribed 16 weeks of elbasvir/grazoprevir and ≥ 1 prescription for ribavirin were included. SVR was defined as HCV RNA below the lower limit of quantification ≥ 70 days after end of treatment. RESULTS: The primary analysis included patients with baseline RASs at positions 30, 31, or 93 (n = 76); a secondary analysis included patients with RASs at positions 28, 30, 31, or 93 (n = 93). SVR was achieved by 77.6% (59/76) of patients in the primary analysis and 80.6% (75/93) of those in the secondary analysis. Of the 18 (19.4%) patients in the secondary cohort who failed to achieve SVR, 8 relapsed (4 with treatment-emergent NS5A substitutions) and 10 did not have viral sequencing to distinguish relapse from reinfection. CONCLUSIONS: This analysis highlights the opportunities in leveraging real-world data to further understand treatment outcomes in smaller, discrete subgroups of patients with HCV infection who cannot be thoroughly evaluated in clinical trials.

Reconstruction of thermoacoustic emission sources induced by proton irradiation using numerical time reversal.

Objective.Mapping of dose delivery in proton beam therapy can potentially be performed by analyzing thermoacoustic emissions measured by ultrasound arrays. Here, a method is derived and demonstrated for spatial mapping of thermoacoustic sources using numerical time reversal, simulating re-transmission of measured emissions into the medium.Approach.Spatial distributions of thermoacoustic emission sources are shown to be approximated by the analytic-signal form of the time-reversed acoustic field, evaluated at the time of the initial proton pulse. Given calibration of the array sensitivity and knowledge of tissue properties, this approach approximately reconstructs the acoustic source amplitude, equal to the product of the time derivative of the radiation dose rate, mass density, and Grüneisen parameter. This approach was implemented using two models for acoustic fields of the array elements, one modeling elements as line sources and the other as rectangular radiators. Thermoacoustic source reconstructions employed previously reported measurements of emissions from proton energy deposition in tissue-mimicking phantoms. For a phantom incorporating a bone layer, reconstructions accounted for the higher sound speed in bone. Dependence of reconstruction quality on array aperture size and signal-to-noise ratio was consistent with previous acoustic simulation studies.Main results.Thermoacoustic source distributions were successfully reconstructed from acoustic emissions measured by a linear ultrasound array. Spatial resolution of reconstructions was significantly improved in the azimuthal (array) direction by incorporation of array element diffraction. Source localization agreed well with Monte Carlo simulations of energy deposition, and was improved by incorporating effects of inhomogeneous sound speed.Significance.The presented numerical time reversal approach reconstructs thermoacoustic sources from proton beam radiation, based on straightforward processing of acoustic emissions measured by ultrasound arrays. This approach may be useful for ranging and dosimetry of clinical proton beams, if acoustic emissions of sufficient amplitude and bandwidth can be generated by therapeutic proton sources.

Classification of accurate and misarticulated /ɑr/ for ultrasound biofeedback using tongue part displacement trajectories.

Ultrasound biofeedback therapy (UBT), which incorporates real-time imaging of tongue articulation, has demonstrated generally positive speech remediation outcomes for individuals with residual speech sound disorder (RSSD). However, UBT requires high attentional demands and may therefore benefit from a simplified display of articulation targets that are easily interpretable and can be compared to real-time articulation. Identifying such targets requires automatic quantification and analysis of movement features relevant to accurate speech production. Our image-analysis program TonguePART automatically quantifies tongue movement as tongue part displacement trajectories from midsagittal ultrasound videos of the tongue, with real-time capability. The present study uses such displacement trajectories to compare accurate and misarticulated American-English rhotic /ɑr/ productions from 40 children, with degree of accuracy determined by auditory perceptual ratings. To identify relevant features of accurate articulation, support vector machine (SVM) classifiers were trained and evaluated on several candidate data representations. Classification accuracy was up to 85%, indicating that quantification of tongue part displacement trajectories captured tongue articulation characteristics that distinguish accurate from misarticulated production of /ɑr/. Regression models for perceptual ratings were also compared. The simplest data representation that retained high predictive ability, demonstrated by high classification accuracy and strong correlation between observed and predicted ratings, was displacements at the midpoint of /r/ relative to /ɑ/ for the tongue dorsum and blade. This indicates that movements of the dorsum and blade are especially relevant to accurate production of /r/, suggesting that a predictive parameter and biofeedback target based on this data representation may be usable for simplified UBT.

Changes in body mass index and clinical outcomes after initiation of contemporary antiretroviral regimens.

BACKGROUND: Weight gain is becoming increasingly prevalent amongst people with HIV (PWH) receiving contemporary antiretroviral treatment. We investigated BMI changes and clinical impact in a large prospective observational study. METHODS: PWH aged ≥18 years were included who started a new antiretroviral (baseline) during 2010-2019 with baseline and ≥1 follow-up BMI assessment available. Rates of clinical outcomes (cardiovascular disease [CVD], malignancies, diabetes mellitus [DM] and all-cause mortality) were analysed using Poisson regression to assess effect of time-updated BMI changes (>1 kg/m 2 decrease, ±1 kg/m 2 stable, >1 kg/m 2 increase), lagged by 1-year to reduce reverse causality. Analyses were adjusted for baseline BMI plus key confounders including antiretroviral exposure. RESULTS: 6721 PWH were included; 72.3% were male, median age 48 years (interquartile range [IQR] 40-55). At baseline, 8.4% were antiretroviral-naive, and 5.0% were underweight, 59.7% healthy weight, 27.5% overweight, and 7.8% were living with obesity. There was an 8.2% increase in proportion of overweight and 4.8% in obesity over the study period (median follow-up 4.4 years [IQR 2.6-6.7]).100 CVDs, 149 malignancies, 144 DMs, and 257 deaths were observed with incidence rates 4.4, 6.8, 6.6, 10.6 per 1000 person-years of follow-up, respectively. Compared to stable BMI, >1 kg/m 2 increase was associated with increased risk of DM (adjusted incidence rate ratio [IRR]: 1.96, 95% confidence interval [CI]: 1.36-2.80) and >1 kg/m 2 decrease with increased risk of death (adjusted IRR: 2.33, 95% CI: 1.73-3.13). No significant associations were observed between BMI changes and CVD or malignancies. CONCLUSIONS: A BMI increase was associated with DM and a decrease associated with death.

Three-dimensional echo decorrelation monitoring of radiofrequency ablation in ex vivo bovine liver.

Three-dimensional (3D) echo decorrelation imaging was investigated for monitoring radiofrequency ablation (RFA) in ex vivo bovine liver. RFA experiments (N = 14) were imaged by 3D ultrasound using a matrix array, with in-phase and quadrature complex echo volumes acquired about every 11 s. Tissue specimens were then frozen at -80 °C, sectioned, and semi-automatically segmented. Receiver operating characteristic (ROC) curves were constructed for assessing ablation prediction performance of 3D echo decorrelation with three potential normalization approaches, as well as 3D integrated backscatter (IBS). ROC analysis indicated that 3D echo decorrelation imaging is potentially a good predictor of local RFA, with the best prediction performance observed for globally normalized decorrelation. Tissue temperatures, recorded by four thermocouples integrated into the RFA probe, showed good correspondence with spatially averaged decorrelation and statistically significant but weak correlation with measured echo decorrelation at the same spatial locations. In tests predicting ablation zones using a weighted K-means clustering approach, echo decorrelation performed better than IBS, with smaller root mean square volume errors and higher Dice coefficients relative to measured ablation zones. These results suggest that 3D echo decorrelation and IBS imaging are capable of real-time monitoring of thermal ablation, with potential application to clinical treatment of liver tumors.

Incidence of Intussusception in Bamako, Mali, Before and After the Introduction of Rotavirus Vaccine.

Pentavalent rotavirus vaccine has been associated with a small increase in intussusception, but pre- and post-introduction data are lacking in many low-resource settings. Using chart review and prospective surveillance data, intussusception incidence was estimated in Bamako, Mali. The mean annual intussusception incidence post-introduction was not significantly different from that of pre-introduction.

Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning.

BACKGROUND AND PURPOSE: The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients. METHODS: Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation. RESULTS: Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65-0.79), 0.76 (95% CI 0.68-0.82) and 0.77 (95% CI 0.70-0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block. CONCLUSION: This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features.

Assessing Vaccine Coverage and Timeliness in Bamako, Mali after the Introduction of Rotavirus Vaccine: A Modified Immunization Cluster Survey.

Vaccine coverage and timeliness are critical metrics for evaluating the performance of immunization programs. Following the introduction of rotavirus vaccine in Bamako, Mali, we conducted two cluster surveys spaced approximately 1 year apart to evaluate these metrics among children 9 to 20 months of age. Using the child's immunization card or the medical record at the center of administration, each selected child's immunization status was determined at 9 and 12 months of age. Deviations from the WHO-recommended immunization schedule were described by the median delay and fraction of children receiving doses outside of recommended age ranges. Overall, 1,002 children were enrolled in the two surveys combined; 80.1% of children born 7 to 12 months after introduction (survey 1) received three doses of pentavalent rotavirus vaccine (ROTA3) by 9 months of age, which increased to 86.1% among children born 17 to 26 months after introduction (survey 2). Concomitantly, coverage with the third dose of diphtheria-pertussis-tetanus-containing vaccine (DPT3) by age 9 months was 86.5% (survey 1) and 88.9% (survey 2); by age 12 months, 61.3% and 72.4% of children, respectively, had received all scheduled immunizations. The median delay in ROTA3 and DPT3 administration were similar at about 3.4 weeks. Within 3 years of introduction, coverage of rotavirus vaccine among Bamako infants achieved coverage similar to DPT3 and is approaching the Global Vaccine Action Plan goal of 90% coverage by 2020. However, timeliness of coverage remains a concern.

Effect of Overpressure on Acoustic Emissions and Treated Tissue Histology in ex Vivo Bulk Ultrasound Ablation.

Bulk ultrasound ablation is a thermal therapy approach in which tissue is heated by unfocused or weakly focused sonication (average intensities on the order of 100 W/cm2) to achieve coagulative necrosis within a few minutes exposure time. Assessing the role of bubble activity, including acoustic cavitation and tissue vaporization, in bulk ultrasound ablation may help in making bulk ultrasound ablation safer and more effective for clinical applications. Here, two series of ex vivo ablation trials were conducted to investigate the role of bubble activity and tissue vaporization in bulk ultrasound ablation. Fresh bovine liver tissue was ablated with unfocused, continuous-wave ultrasound using ultrasound image-ablate arrays sonicating at 31 W/cm2 (0.9 MPa amplitude) for either 20 min at a frequency of 3.1 MHz or 10 min at 4.8 MHz. Tissue specimens were maintained at a static overpressure of either 0.52 or 1.2 MPa to suppress bubble activity and tissue vaporization or at atmospheric pressure for control groups. A passive cavitation detector was used to record subharmonic (1.55 or 2.4 MHz), broadband (1.2-1.5 MHz) and low-frequency (5-20 kHz) acoustic emissions. Treated tissue was stained with 2% triphenyl tetrazolium chloride to evaluate thermal lesion dimensions. Subharmonic emissions were significantly reduced in overpressure groups compared with control groups. Correlations observed between acoustic emissions and lesion dimensions were significant and positive for the 3.1-MHz series, but significant and negative for the 4.8-MHz series. The results indicate that for bulk ultrasound ablation, where both acoustic cavitation and tissue vaporization are possible, bubble activity can enhance ablation in the absence of tissue vaporization, but can reduce thermal lesion dimensions in the presence of vaporization.

Planning for monitoring the introduction and effectiveness of new vaccines using real-word data and geospatial visualization: An example using rotavirus vaccines with potential application to SARS-CoV-2.

BACKGROUND: Infectious diseases continue to cause significant impact on human health. Vaccines are instrumental in preventing infectious diseases and mitigating pandemics and epidemics. SARS-CoV-2 is the most recent example of an urgent pandemic that requires the development of vaccines. This study combined real-world data and geospatial visualization techniques to demonstrate methods to monitor and communicate the uptake and impact of existing and new vaccines. METHODS: Observational data of existing pediatric rotavirus vaccines were used as an example. A large US national insurance claims database was accessed to build an analytic dataset for a 20-year period (1996-2017). For each week and multiple geographic scales, animated spatial and non-spatial visualization techniques were applied to demonstrate changes in seasonal rotavirus epidemic curves and population-based disease rates before, during, and after vaccine introduction in 2006. The geographic scales included national, state, county and zip code tabulation areas. An online web-based digital atlas was built to display either continuous or snapshot visualizations of disease patterns, vaccine uptake, and improved health outcomes after vaccination (http://www.mapvaccines.com). RESULTS: Over 17 million zip code-weeks of data were available for analysis. The animations show geospatial patterns of rotavirus-related medical encounter rates peaking every year from November - February prior to vaccine availability in 2006. Visualizations showed increasing vaccination coverage rates at all geographic scales over time. Declines in medical encounter rates accelerated as vaccination coverage rapidly increased after 2010. The data maps also identified geographic hotspots with low vaccination rates and persistent disease rates. CONCLUSION: This project developed novel web-based methods to communicate location and time-based vaccine uptake and the related reduction in medical visits due to viral infection. Future applications of the visualization could be used by health agencies to monitor known or novel disease patterns over time in conjunction with close assessment of current and future vaccine utilization.

Reconstruction of shear wave speed in tissue-mimicking phantoms from aliased pulse-echo imaging of high-frequency wavefields.

Quantitative elasticity estimation in medical and industrial applications may benefit from advancements in reconstruction of shear wave speed with enhanced resolution. Here, shear wave speed is reconstructed from pulse-echo ultrasound imaging of elastic waves induced by high-frequency (>400 Hz), time-harmonic mechanical excitation. Particle displacement in shear wavefields is mapped from measured interframe phase differences with compensation for timing of multiple scan lines, then processed by spatial Fourier analysis to estimate the predominant wave speed and analyzed by algebraic wavefield inversion to reconstruct wave speed maps. Reconstructions of shear wave speed from simulated wavefields illustrate the accuracy and spatial resolution available with both methods, as functions of signal-to-noise ratio and sizes of windows used for Fourier analysis or wavefield smoothing. The methods are applied to shear wavefields with frequencies up to six times the Nyquist rate, thus extending the frequency range measurable by a given imaging system. Wave speed measurements in tissue-mimicking phantoms are compared with supersonic shear imaging and mechanical tensile testing, demonstrating feasibility of the wavefield measurement and wave speed reconstruction methods employed.

CMV viral load kinetics as surrogate endpoints after allogeneic transplantation.

BACKGROUNDViral load (VL) surrogate endpoints transformed development of HIV and hepatitis C therapeutics. Surrogate endpoints for CMV-related morbidity and mortality could advance development of antiviral treatments. Although observational data support using CMV VL as a trial endpoint, randomized controlled trials (RCTs) demonstrating direct associations between virological markers and clinical endpoints are lacking.METHODSWe performed CMV DNA PCR on frozen serum samples from the only placebo-controlled RCT of ganciclovir for early treatment of CMV after hematopoietic cell transplantation (HCT). We used established criteria to assess VL kinetics as surrogates for CMV disease or death by weeks 8, 24, and 48 after randomization and quantified antiviral effects captured by each marker. We used ensemble-based machine learning to assess the predictive ability of VL kinetics and performed this analysis on a ganciclovir prophylaxis RCT for validation.RESULTSVL suppression with ganciclovir reduced cumulative incidence of CMV disease and death for 20 years after HCT. Mean VL, peak VL, and change in VL during the first 5 weeks of treatment fulfilled the Prentice definition for surrogacy, capturing more than 95% of ganciclovir's effect, and yielded highly sensitive and specific predictions by week 48. In the prophylaxis trial, the viral shedding rate satisfied the Prentice definition for CMV disease by week 24.CONCLUSIONSOur results support using CMV VL kinetics as surrogates for CMV disease, provide a framework for developing CMV preventative and therapeutic agents, and support reductions in VL as the mechanism through which antivirals reduce CMV disease.FUNDINGMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Numerical analysis of three-dimensional echo decorrelation imaging.

A numerical model for three-dimensional echo decorrelation imaging, a pulse-echo ultrasound method applicable to thermal ablation monitoring, is presented. Beam patterns for steered transmit and receive array apertures are combined with a three-dimensional numerical tissue model to yield beamformed scan lines in a pyramidal configuration, volumetric B-mode images, and spatial maps of normalized decorrelation between sequential image volumes. Simulated three-dimensional echo decorrelation images of random media are analyzed as estimators of local tissue reflectivity decoherence, mimicking thermal ablation effects. The estimation error is analyzed as a function of correlation window size, scan line density, and ensemble averaging of decorrelation maps.

In vivo ultrasound thermal ablation control using echo decorrelation imaging in rabbit liver and VX2 tumor.

The utility of echo decorrelation imaging feedback for real-time control of in vivo ultrasound thermal ablation was assessed in rabbit liver with VX2 tumor. High-intensity focused ultrasound (HIFU) and unfocused (bulk) ablation were performed using 5 MHz linear image-ablate arrays. Treatments comprised up to nine lower-power sonications, followed by up to nine higher-power sonications, ceasing when the average cumulative echo decorrelation within a control region of interest exceeded a predefined threshold (- 2.3, log10-scaled echo decorrelation per millisecond, corresponding to 90% specificity for tumor ablation prediction in previous in vivo experiments). This threshold was exceeded in all cases for both HIFU (N = 12) and bulk (N = 8) ablation. Controlled HIFU trials achieved a significantly higher average ablation rate compared to comparable ablation trials without image-based control, reported previously. Both controlled HIFU and bulk ablation trials required significantly less treatment time than these previous uncontrolled trials. Prediction of local liver and VX2 tumor ablation using echo decorrelation was tested using receiver operator characteristic curve analysis, showing prediction capability statistically equivalent to uncontrolled trials. Compared to uncontrolled trials, controlled trials resulted in smaller thermal ablation regions and higher contrast between echo decorrelation in treated vs. untreated regions. These results indicate that control using echo decorrelation imaging may reduce treatment duration and increase treatment reliability for in vivo thermal ablation.

The effect of 220 kHz insonation scheme on rt-PA thrombolytic efficacy in vitro.

Ultrasound-enhanced recombinant tissue plasminogen activator (rt-PA) thrombolysis is under development as an adjuvant to ischemic stroke therapy. The goal of this study was to design a pulsed ultrasound (US) exposure scheme that reduced intracranial constructive interference and tissue heating, and maintained thrombolytic efficacy relative to continuous wave (CW) insonation. Three 220 kHz US schemes were evaluated, two pulsed insonation schemes (15 cycles, 68 µs pulse duration, 33% or 62.5% duty cycle) and an intermittent CW insonation scheme (50 s active, 30 s quiescent) over a 30-min treatment period. An in silico study using a finite-difference model of transcranial US propagation was performed to estimate the intracranial acoustic field and temperature rise in the skull for each insonation scheme. In vitro measurements with flow were performed to assess thrombolysis using time-lapse microscopy. Intracranial constructive interference was not reduced with pulsed US using a pulse length of 15 cycles compared to intermittent CW US. The 33.3% duty cycle pulsed US scheme reduced heating in the temporal bone as much as 60% relative to the intermittent CW scheme. All insonation schemes promoted sustained stable cavitation in vitro and augmented thrombolysis compared to rt-PA alone (p  < 0.05). Ultraharmonic (UH) and harmonic cumulative energy over a 30 min treatment period was significantly higher (p  < 0.05) for the intermittent CW US scheme compared to either pulsed US scheme. Despite the difference in cavitation emissions, no difference was observed in the clot lysis between the three US schemes. These findings demonstrate that a 33.3% duty cycle pulsed US scheme with a 15-cycle burst can reduce bone heating and achieve equivalent thrombolytic efficacy as an intermittent CW scheme.

The Netherlands Arrhythmogenic Cardiomyopathy Registry: design and status update.

BACKGROUND: Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions. AIM: To create a large national ACM patient cohort with a vast amount of uniformly collected high-quality data that is readily available for future research. METHODS: This is a multicentre, longitudinal, observational cohort study that includes (1) patients with a definite ACM diagnosis, (2) at-risk relatives of ACM patients, and (3) ACM-associated mutation carriers. At baseline and every follow-up visit, a medical history as well information regarding (non-)invasive tests is collected (e. g. electrocardiograms, Holter recordings, imaging and electrophysiological studies, pathology reports, etc.). Outcome data include (non-)sustained ventricular and atrial arrhythmias, heart failure, and (cardiac) death. Data are collected on a research electronic data capture (REDCap) platform in which every participating centre has its own restricted data access group, thus empowering local studies while facilitating data sharing. DISCUSSION: The Netherlands ACM Registry is a national observational cohort study of ACM patients and relatives. Prospective and retrospective data are obtained at multiple time points, enabling both cross-sectional and longitudinal research in a hypothesis-generating approach that extends beyond one specific research question. In so doing, this registry aims to (1) increase the scientific knowledge base on disease mechanisms, genetics, and novel diagnostic and treatment strategies of ACM; and (2) provide education for physicians and patients concerning ACM, e. g. through our website ( www.acmregistry.nl ) and patient conferences.